Neuroimaging, cognition, light and circadian rhythms

Abstract

In humans, sleep and wakefulness and the associated cognitive processes are regulated through interactions between sleep homeostasis and the circadian system. Chronic disruption of sleep and circadian rhythmicity is common in our society and there is a need for a better understanding of the brain mechanisms regulating sleep, wakefulness and associated cognitive processes. This review summarizes recent investigations which provide first neural correlates of the combined influence of sleep homeostasis and circadian rhythmicity on cognitive brain activity. Markers of interindividual variations in sleep-wake regulation, such as chronotype and polymorphisms in sleep and clock genes, are associated with changes in cognitive brain responses in subcortical and cortical areas in response to manipulations of the sleep-wake cycle. This review also includes recent data showing that cognitive brain activity is regulated by light, which is a powerful modulator of cognition and alertness and also directly impacts sleep and circadian rhythmicity. The effect of light varied with age, psychiatric status, PERIOD3 genotype and changes in sleep homeostasis and circadian phase. These data provide new insights into the contribution of demographic characteristics, the sleep-wake cycle, circadian rhythmicity and light to brain functioning.

Keywords: circadian; cognition; fMRI; inter-individual differences in sleep-wake regulation; light; non-image-forming; non-visual; sleep.

Figure 1

Morning and evening chronotypes differ in their brain responses to an attentional task and SWA. (A) Exponential decay function adjusted on relative SWA in sleep cycles (NREM sleep) measured from the central frontal derivation for all-night EEG of the night preceding the evening scan acquisition. (B) Increased task-related response in the dorsal pontine tegmentum and the anterior hypothalamus, compatible with the locus coeruleus (LC) and suprachiasmatic area (SCA) respectively, in evening as compared to morning chronotypes during the subjective evening for optimal sustained attention during the performance of a Psychomotor Vigilance Task (PVT). Corresponding activity estimates (arbitrary units—a.u. +/− sem) are displayed for event indicators of fast reaction times. (C) Regression analysis of the relation between estimated blood oxygen level-dependent (BOLD) responses during optimal task performance in the SCA region and the amount of SWA during the first sleep cycle in the preceding night (r = 0.54, p < 0.05, n = 27). Red crosses: morning types, blue triangles: evening types. [Copied with permission from Schmidt et al. (2009); Cajochen et al. (2010)].

Figure 2

Impact of the interaction between homeostatic sleep pressure and circadian process on cognitive performance in PER3^4/4 (blue line) and PER3^5/5 (red line) individuals. (A) As indicated by slow wave activity (SWA) measure, PER3^5/5 have a faster build-up during wakefulness and a quicker dissipation during sleep of homeostatic sleep pressure (based on data from Viola et al. (2007)). (B) Regarding circadian phase, PER3^4/4 and PER3^5/5 do not appear to differ, as indicated by melatonin, cortisol, and PER3 mRNA measures (based on data from Viola et al. (2007)). Note that the circadian signal increasingly promotes wakefulness during the day (positive value, above horizontal line) and increasingly promotes sleep during the night (negative value, below horizontal line). (C) Theoretical modulation of the circadian signal by homeostatic sleep pressure in both PER3 genotypes. The difference in homeostatic sleep pressure results in a limited difference in the output of this interaction during a normal waking day. The output of the interaction affects much more negatively wakefulness of PER3^5/5 in the absence of overnight sleep, particularly in the early morning hours when the circadian system maximally promotes sleep. (D) Composite measures of performance in both PER3 genotypes, based on extended neurophychological test batteries (Viola et al., 2007). Performance profile closely follow theoretical interaction between circadian and sleep homeostasis processes depicted in C. This model could speculatively be applied to extremes morning and evening chronotypes, which also differ in term of homeostatic sleep pressure build up (Mongrain and Dumont, 2007) (but also they differ sometimes in term of circadian phase angle with sleep (Mongrain et al., 2006a)). [Copied with permission from Dijk and Archer (2010)].

Figure 3

Difference between PER3^4/4 and PER3^5/5 individuals in the sleep loss-induced changed in brain responses to a working memory task. When comparing brain responses to an auditory 3-back task in the morning after a night of sleep (MS 1.5 h of wakefulness) and in the morning after a night of sleep deprivation (MSD 25 h of wakefulness), PER3^5/5 individuals undergo marked decreases in activation in several brain areas of the occipital (1, 2) and temporal (3, 4) cortices, and of the dorsolateral prefrontal (5, 6) and parietal cortex (7–9), while PER3^4/4 individuals maintain brain responses in these areas (and do not present significant decreased activations in any brain regions). A representative profile of this brain activity change is displayed in panel A (similar profiles were observed for red areas 1–9). In contrast, when comparing the same sessions, PER3^4/4 individuals present increased activation (blue) in the parahippocampus (10), superior colliculus (11), temporal cortex (12), pulvinar (13), and ventrolateral prefrontal cortex (14), while no increased activation is observed in these regions in PER3^5/5 (and in any other brain regions). A representative profile of this brain activity change is displayed in panel B (similar profiles were observed for blue areas 10–14). A significant negative association was found between overnight change in brain response in the pulvinar (green circle) and self-reported daytime propensity to fall asleep in everyday life across all the subjects of the study (irrespective of genotype), further suggesting a central role for the pulvinar in wakefulness regulation. [Adapted with permission from Vandewalle et al. (2009a)].

Figure 4

Schematic representation of the brain mechanisms involved in the non-image-forming impact of light on cognitive brain responses. (1) Responses at light onset are found within the hypothalamus (blue) and pulvinar (green) (and amygdala and hippocampus, not shown); (2) within the first seconds of the exposure, responses are found mainly in subcortical and cortical structures involved in alertness regulation (hypothalamus, brainstem (yellow), pulvinar); (3) late responses are detected at the cortical level in areas involved in the ongoing cognitive process and can subsequently affect performance. For attention/working memory/executive task (red) a network of areas around the pulvinar and including prefrontal and parietal areas appear to mediate the impact of light on alertness and cognition. For emotional responses to vocal stimuli (light blue), the network involves the hypothalamus, amygdala, and voice-sensitive area of the temporal cortex. Light seems to have a swifter impact on emotional cortical responses than attentional/working memory/executive responses. The impact of light is stronger with higher intensity, longer duration, and shorter wavelength (blue) light exposures. Time of day and the associated changes in the interaction between circadian and sleep homeostasis signals and PERIOD3 genotype modulate the impact of light. [Adapted with permission from Vandewalle et al. (2009b)].

Figure 5

Endogenous and exogenous regulation of sleep and wakefulness affects cognitive brain responses through overlapping pathways. Blue light increases cognitive brain responses in regions showing decreased activation (PER3^5/5) or compensatory recruitment (PER3^4/4) in darkness, following sleep loss. Blue solid: compensatory increase in activation in the morning hours after 25 h of wakefulness in PER3^4/4, found in the ventrolateral prefrontal cortex, temporal cortex, cerebellum, and thalamus (not shown). Red solid: decreases in activation in the morning hours after 25 h of wakefulness in PER3^5/5, observed in the occipital, temporal, parietal, and lateral prefrontal cortices. Red open: blue light-induced increase in activations after 25 h of wakefulness in PER3^5/5(thalamus not shown). Blue open: blue light-induced increase in activity after 1.5 h of wakefulness in PER3^4/4. DLPFC = dorsolateral prefrontal cortex; FPC / VLPFC = frontopolar / ventrolateral prefrontal cortex; IPS = intraparietal sulcus; PMOT = premotor cortex. [Copied with permission from Vandewalle et al. (2011a)].